Process for preparing phosphorus containing cyanohydrins

ABSTRACT

The present invention relates primarily to a process for preparing certain phosphorus-containing cyanohydrins of the formula (I), and also to certain phosphorus-containing cyanohydrins per se and to their use for the preparation of glufosinate and/or glufosinate salts. The present invention further relates to certain mixtures particularly suitable for preparing the phosphorus-containing cyanohydrins of the formula (I).

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. application Ser.No. 15/310,566, filed Nov. 11, 2016, which is a § 371 National StageApplication of PCT/EP2015/060211, filed May 8, 2015, which claimspriority to European Application No. 14168134.6 filed May 13, 2014, thecontents of each are incorporated herein in their entireties.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates primarily to a process for preparingcertain phosphorus-containing cyanohydrins of the formula (I) definedbelow, and also to certain phosphorus-containing cyanohydrins per se andto their use for the preparation of glufosinate and/or glufosinatesalts. The present invention further relates to certain mixturesparticularly suitable for preparing the phosphorus-containingcyanohydrins of the formula (I) defined below.

Description of Related Art

Phosphorus-containing cyanohydrins are useful intermediates in a varietyof subject fields, more particularly for the production of biologicallyactive substances which can be used in the pharmaceutical and/oragrochemical sector.

U.S. Pat. No. 4,168,963 describes diverse phosphorus-containingcompounds with herbicidal activity, of which, in particular,phosphinothricin (2-amino-4-[hydroxy(methyl)phosphinoyl]butanoic acid;common name: glufosinate) and its salts have acquired commercialimportance in the agrochemistry (agricultural chemistry) sector.

Methods for producing intermediates for the synthesis ofphosphorus-containing compounds of this kind with herbicidal activity,more particularly glufosinate, are described in U.S. Pat. No. 4,521,348,DE 3047024, U.S. Pat. Nos. 4,599,207 and 6,359,162B1, for example.

CN 102372739A describes a process for preparing glufosinate by reacting(3-cyano-3-hydroxypropyl)-methylphosphinic acid with carbon dioxide,ammonia and water.

CN 102399240A discloses processes for preparing glufosinate andglufosinate analogs, the starting materials therein including PCl₃,CH₃MgCl and certain trialkyl esters of phosphorous acid. The dialkylmethylphosphonates and alkyl methyphosphinates prepared therefrom aresubsequently reacted therein by Michael addition and further reactionsteps to form glufosinate and glufosinate analogs.

CN 101830926A relates to the preparation of dialkylmetal phosphinatesand to the use thereof as flame retardants. In the process described,alkyl phosphinates are reacted with terminal olefins, the reactionsincluding that of monobutyl methanephosphinate with cyclohexene.

The processes from the prior art for preparing phosphorus-containingcyanohydrins have disadvantages: for example, an inadequate yield ofphosphorus-containing cyanohydrins, an excessive fraction of co-productsor secondary products, an excessive cost and complexity in purifyingand/or isolating the phosphorus-containing cyanohydrins, and/or reactionconditions which are too harsh or too difficult in terms of processand/or equipment.

SUMMARY

It was an object of the present invention, therefore, to find a processfor preparing phosphorus-containing cyanohydrins that affords thephosphorus-containing cyanohydrins in a very good yield.

The process ought preferably to fulfill simultaneously one, two or more,or all of the following aspects (i) to (iv):

(i) maximum ease of implementation in terms of process and/or equipment;

(ii) mild reaction conditions;

(iii) very low fraction of secondary products (that are difficult toremove);

(iv) extremely simple purification and/or isolation of thephosphorus-containing cyanohydrins.

This object is fulfilled by the process of the invention as describedhereinafter.

The present invention provides a process for preparingphosphorus-containing cyanohydrins of the formula (I)

characterized in that a compound of the formula (II)

is reacted with a cyanohydrin of the formula (III)

at a temperature in the range from 50 to 105° C., preferably at atemperature in the range from 60 to 95° C., more preferably at atemperature in the range from 65 to 90° C.,

where in each case:

-   -   R¹ is (C₁-C₁₂)-alkyl, (C₁-C₁₂)-haloalkyl, (C₆-C₁₀)-aryl,        (C₆-C₁₀)-haloaryl, (C₇-C₁₀)-aralkyl, (C₇-C₁₀)-haloaralkyl,        (C₄-C₁₀)-cycloalkyl or (C₄-C₁₀)-halocycloalkyl,    -   R² is (C₁-C₁₂)-alkyl, (C₁-C₁₂)-haloalkyl, (C₆-C₁₀)-aryl,        (C₆-C₁₀)-haloaryl, (C₇-C₁₀)-aralkyl, (C₇-C₁₀)-haloaralkyl,        (C₄-C₁₀)-cycloalkyl or (C₄-C₁₀)-halocycloalkyl,    -   R³ and R⁴ are in each case independently of one another        hydrogen, (C₁-C₄)-alkyl, phenyl or benzyl,    -   X is oxygen or sulphur, and    -   n is 0 or 1.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT

DE 3047024 describes in principle the reaction of compounds of theformula (II) with compounds of the formula (III) to form compounds ofthe formula (I), but in an unsatisfactory yield, which is inadequate inparticular on the industrial or plant scale. By way of example, DE3047024 describes the reaction of monoisobutyl methanephosphonate withacrolein cyanohydrin with addition of a catalytic amount of a“peroctoate” radical initiator at a temperature of 120-130° C. The yieldafter distillation there was 79% of theory.

The cyanohydrins of the formula (III) have a significantly higherreactivity than the corresponding compounds which have an O-acetyl groupinstead of the free hydroxyl group, of the kind used in U.S. Pat. Nos.4,521,348 or 4,599,207, for example.

With the process of the invention, in which the reaction temperature isheld within the temperature range defined in accordance with theinvention, and in which preferably radical initiators of the formula(IV) defined below are used, the phosphorus-containing cyanohydrins ofthe formula (I) are obtained in significantly better yield and generallyin higher purity.

The compounds of the formula (III) used in the process of the inventiondo not have an O-acetyl group, and the further glufosinate preparationprocess of the invention described below, in contrast to the processesdescribed in U.S. Pat. Nos. 4,521,348 or 4,599,207, does not produce anyacetic acid or acetic acid derivatives as accompanying components orco-products.

It has further emerged that in the process of the invention forpreparing the compound of the formula (I) (and also the compound of theformula (Ia) or (Ib) defined below), the quality of the unreacted andrecovered—that is, recycled—amount of the compound of the formula (II)(or of the formula (IIa) or (IIb) defined below) after reaction hastaken place is better than in the processes known from the literaturewhere, rather than the cyanohydrins of the formula (III), thecorresponding O-acetylated cyanohydrins are used.

Recovered (recycled) quantities of the compound of the formula (II) fromthe processes known from the literature that use, rather than thecyanohydrins of the formula (III), the corresponding O-acetylatedcyanohydrins customarily contain marked fractions (about 5 wt %) ofacetic acid, which are impossible to remove without considerabledistillative cost and complexity. But residual amounts of acetic acidinhibit or slow down the radical reaction, rendering it disadvantageousto return the recovered (recycled) quantities of the compound of theformula (II) into the radical reaction and to use them again in thatreaction.

Overall, in the process of the invention, and in the further processesof the invention described below for the preparation of glufosinate,fewer unwanted secondary components are formed, and so the processes ofthe invention are more efficient and more energy-saving.

The respective alkyl radicals of the radicals R¹, R², R³ and R⁴ may ineach case be straight-chain or branched-chain (branched) in the carbonscaffold.

The expression “(C₁-C₄)-alkyl” here is the abbreviated notation for analkyl radical having 1 to 4 carbon atoms, therefore encompassing theradicals methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl,2-methylpropyl or tert-butyl. Correspondingly, general alkyl radicalswith a greater stated range of C atoms, as for example “(C₁-C₆)-alkyl”,also encompass straight-chain or branched alkyl radicals having agreater number of C atoms, i.e., according to example, the alkylradicals also having 5 and 6 C atoms.

“Halogen” pertains preferably to the group consisting of fluorine,chlorine, bromine and iodine. Haloalkyl, haloaryl, haloaralkyl andhalocycloalkyl denote alkyl, aryl, aralkyl and cycloalkyl, respectively,that are partly or wholly substituted by identical or different halogenatoms, preferably from the group of fluorine, chlorine and bromine, moreparticularly from the group of fluorine and chlorine. Thus, for example,haloalkyl encompasses monohaloalkyl (=monohalogenoalkyl), dihaloalkyl(=dihalogenoalkyl), trihaloalkyl (=trihalogenoalkyl), or elseperhaloalkyl, such as, for example, CF₃, CHF₂, CH₂F, CF₃CF₂, CH₂FCHCl,CCl₃, CHCl₂, CH₂CH₂Cl. Corresponding comments apply to the otherradicals substituted by halogen.

Suitable and preferred compounds of the formula (II) include thefollowing: methanephosphonous acid mono(C₁-C₆)-alkyl esters, monododecylmethanephosphonate, monophenyl methanephosphonate; ethane-phosphonousacid mono(C₁-C₆)-alkyl esters, monododecyl ethanephosphonate, monophenylethane-phosphonate; propanephosphonous acid mono(C₁-C₆)-alkyl esters,monododecyl propanephosphonate, monophenyl propanephosphonate;butanephosphonous acid mono(C₁-C₆)-alkyl esters, monododecylbutanephosphonate, monophenyl butanephosphonate; phenylphosphonous acidmono(C₁-C₆)-alkyl esters, monododecyl phenylphosphonate, monophenylphenylphosphonate; benzylphosphonous acid mono-(C₁-C₆)-alkyl esters,monododecyl benzylphosphonate, monophenyl benzylphosphonate;methylthio-phosphonous acid mono(C₁-C₆)-alkyl esters, monododecylmethylthiophosphonate, monophenyl methyl-thiophosphonate;dimethylphosphine oxide, diethylphosphine oxide, dipropylphosphineoxide, dibutyl-phosphine oxide, diphenylphosphine oxide,methylphenylphosphine oxide, dibenzylphosphine oxide, dimethylphosphinesulphide, and diphenylphosphine sulphide.

The preparation of the compounds of the formula (II) is known to theskilled person and can take place in accordance with processes knownfrom the literature (e.g. U.S. Pat. Nos. 3,914,345; 4,474,711;4,485,052; 4,839,105; 5,128,495).

Suitable and preferred cyanohydrins of the formula (III) include thefollowing: acrolein cyanohydrin, methacrolein cyanohydrin, ethacroleincyanohydrin, and phenyl vinyl ketone cyanohydrin.

The preparation of the cyanohydrins of the formula (III) is known to theskilled person and can take place in accordance with processes knownfrom the literature (e.g. from U.S. Pat. Nos. 3,850,976 or 4,336,206).

For the process of the invention, the following is preferably the case:

R³ and R⁴ are in each case independently of one another hydrogen ormethyl,

and/or

X is oxygen,

and/or

n is 1.

The process of the invention relates preferably to the preparation ofphosphorus-containing cyanohydrins of the formula (Ia)

characterized in that a compound of the formula (IIa)

is reacted with acrolein cyanohydrin of the formula (IIIa)

at a temperature in the range from 50 to 105° C., preferably at atemperature in the range from 60 to 95° C., more preferably at atemperature in the range from 65 to 90° C.,

where in each case:

-   -   R¹ is (C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl, (C₆-C₈)-aryl,        (C₆-C₈)-haloaryl, (C₇-C₁₀)-aralkyl, (C₇-C₁₀)-haloaralkyl,        (C₅-C₈)-cycloalkyl or (C₅-C₈)-halocycloalkyl,    -   R² is (C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl, (C₆-C₈)-aryl,        (C₆-C₈)-haloaryl, (C₇-C₁₀)-aralkyl, (C₇-C₁₀)-haloaralkyl,        (C₅-C₈)-cycloalkyl or (C₅-C₈)-halocycloalkyl.

Preferably in each case:

-   -   R¹ is (C₁-C₄)-alkyl or (C₁-C₄)-haloalkyl, preferably methyl or        ethyl,    -   R² is (C₁-C₆)-alkyl or (C₁-C₆)-haloalkyl, preferably        (C₃-C₆)-alkyl, in turn preferably C₄-alkyl or C₅-alkyl.

More preferably in each case:

-   -   R¹ is methyl,    -   R² is C₄-alkyl or C₅-alkyl, preferably n-butyl or n-pentyl,

i.e. particular preference is given to using compounds of the formula(IIb)

where R² is n-butyl or n-pentyl.

The process of the invention is preferably carried out under conditionsin which free radicals are formed.

The reaction of the compounds of the formula (II) and (III) or (IIa) and(IIIa) to give the compounds of the formula (I) or (Ia), respectively,in a process of the invention takes place preferably with the aid of aradical-forming radiation source (such as UV, gamma or X-rays) or in thepresence of one or more radical-forming substances.

For the purposes of the process of the invention, preference is given tousing radical-forming substances, more preferably radical initiators ofthe formula (IV) defined below:

where

-   -   R⁵ is methyl, ethyl, 2,2-dimethylpropyl or phenyl,    -   R⁶ independently at each occurrence is (C₁-C₁₀)-alkyl,        preferably (C₁-C₆)-alkyl, more preferably (C₁-C₄)-alkyl,

and

-   -   R⁷ is hydrogen or (C₁-C₁₀)-alkyl, preferably hydrogen or        (C₁-C₆)-alkyl, more preferably hydrogen or (C₁-C₄)-alkyl.

The radical initiators of the formula (IV) are known per se and some ofthem are available commercially.

The radical initiators of the formula (IV) are preferably selected fromthe group consisting of tert-butyl peroxypivalate, tert-amylperoxypivalate, tert-butyl peroxyneodecanoate, 1,1,3,3-tetramethylbutylperoxy-neodecanoate, tert-butylperoxy-2-ethylhexanoate,1,1,3,3-tetramethylbutyl peroxy-2-ethylhexanoate, tert-amylperoxyneodecanoate, cumyl peroxyneodecanoate, cumyl peroxyneoheptanoate,cumyl peroxy-pivalate, and mixtures thereof.

The radical initiators of the formula (IV) are preferably selected fromthe group consisting of tert-butylperoxyneodecanoate,1,1,3,3-tetramethylbutyl peroxyneodecanoate,tert-butylperoxy-2-ethyl-hexanoate, 1,1,3,3-tetramethylbutylperoxy-2-ethylhexanoate, cumyl peroxyneodecanoate, and mixtures thereof,more preferably in turn 1,1,3,3-tetramethylbutyl peroxyneodecanoate,tert-butyl peroxyneodecanoate and/or tert-butylperoxy-2-ethylhexanoate.

The radical initiators stated as preferred, in particular, permit a verygood reaction regime under mild reaction conditions, more particularlywithin the temperature range stated as preferred, thereby allowing thedesired phosphorus-containing cyanohydrins of the formula (I) and (Ia)to be obtained in high yields and high purity.

Preference is given to using a total of 0.1 to 10 mol %, more preferably0.25 to 7 mol %, even more preferably 0.5 to 7 mol %, especiallypreferably 0.5 to 5 mol %, of radical initiators of the formula (IV),based on the total amount of cyanohydrin of the formula (III) or (IIIa)that is used.

The radical initiator of the formula (IV), or a mixture of radicalinitiators of the formula (IV), may be mixed together with thecyanohydrin of the formula (III) or (IIIa), and the mixture meteredin—that is, added under dosage control—to the initially introducedcompound of the formula (II) or (IIa). Alternatively, the radicalinitiator or a mixture of radical initiators of the formula (IV) mayalso be mixed with the phosphorus-containing reactant (II) or (IIa) oradded, under dosage control, in pure form simultaneously separatelyalongside the cyanohydrin of the formula (III) or (IIIa).

The radical initiator or a mixture of radical initiators of the formula(IV) is preferably mixed with the phosphorus-containing reactant (II) or(IIa) or may also be added under dosage control in pure formsimultaneously separately alongside the cyanohydrin of the formula (III)or (IIIa). Alternatively, the radical initiator of the formula (IV), ora mixture of radical initiators of the formula (IV), may also be mixedtogether with the cyanohydrin of the formula (III) or (IIIa), and themixture metered in—that is, added under dosage control—to the initiallyintroduced compound of the formula (II) or (IIa).

Where a “portion” is referred to in the observations hereinafter, onlypart of the total amount used in the process of the invention is used inthe procedure defined at that particular point.

The process of the invention can be carried out such that the radicalinitiator or initiators of the formula (IV), or a portion of the radicalinitiator or initiators of the formula (IV), is premixed with a portionor the entirety of the compound (III) or (IIIa) (“mixture IV+III”),

and this mixture, i.e. “mixture IV+III”, is metered into the reactionvessel.

The process of the invention is preferably carried out such that

compound (III) or (IIIa) is premixed with a portion of the compound (II)or (IIa) (“mixture III+II”),

spatially separately therefrom (i.e. in a separate container), a portionof the compound (II) or (IIa) is premixed with the radical initiator(IV) (“mixture II+IV”),

and these two mixtures, i.e. “mixture III+II” and “mixture II+IV”, aremetered simultaneously into the reaction vessel.

With the preferred procedures below, the phosphorus-containingcyanohydrins of the formula (I) or (Ia) are obtained particularlyeffectively and in even better yield.

The process of the invention is preferably carried out, accordingly,such that the radical initiator or initiators of the formula (IV) or aportion of the radical initiator or initiators of the formula (IV) is orare premixed with a portion or the entirety of the compound (II) or(IIa) (“mixture IV+II”), and this mixture, i.e. “mixture IV+II”, ismetered simultaneously with and separately from the compound of theformula (III) or (IIIa) into the reaction vessel.

Compound of the formula (III) or (IIIa) here is preferably metered intothe reaction vessel from a separate container that constitutes aseparate construction.

In the case of the batch mode, and depending in that case on the batchsize, the simultaneous metering in each of the abovementioned procedureslasts preferably for longer than 30 minutes, more preferably 30 minutesto 20 hours, very preferably 1 to 12 hours.

The above-defined mixtures “mixture IV+III”, “mixture IV+II”, “mixtureIII+II”, and “mixture II+IV” are likewise provided by the presentinvention.

The present invention consequently also relates to a mixture selectedfrom the group consisting of

mixture comprising one or more compounds of the formula (IV) and one ormore compounds of the compound (III) formula,

mixture comprising one or more compounds of the formula (IV) and one ormore compounds of the compound (II) formula,

mixture comprising one or more compounds of the formula (III) and one ormore compounds of the compound (II) formula, wherein such a mixturepreferably contains no compound of the above-defined formula (IV) and/orno compound of the above-defined formula (I),

wherein the compounds of the formula (II), (III) and (IV) each have thestructure defined above, preferably in each case a structure definedabove as preferred or particularly preferred.

The present invention preferably relates to a mixture selected from thegroup consisting of

mixture comprising one or more compounds of the formula (IV) and one ormore compounds of the compound (III) formula,

mixture comprising one or more compounds of the formula (IV) and one ormore compounds of the compound (II) formula,

wherein the compounds of the formula (II), (III) and (IV) each have thestructure defined above, preferably in each case a structure definedabove as preferred or particularly preferred.

For the mixtures of the invention it is preferably the case that thecompounds of the formula (II) and the compounds of the formula (III) areselected from the group of the compounds of the formula (IIa) and fromthe group of the compounds of the formula (IIIa), with the compounds ofthe formula (IIa) and/or (IIb) and also (IIIa) defined above aspreferred being preferred in turn.

Preferred mixtures of the invention comprise or consist of

-   -   one or more radical initiators of the formula (IV) selected from        the group consisting of tert-butyl peroxypivalate, tert-amyl        peroxypivalate, tert-butyl peroxyneodecanoate,        1,1,3,3-tetramethylbutyl peroxyneodecanoate,        tert-butylperoxy-2-ethylhexanoate, 1,1,3,3-tetramethylbutyl        peroxy-2-ethyl-hexanoate, tert-amyl peroxyneodecanoate, cumyl        peroxyneodecanoate, cumyl peroxyneoheptanoate, and cumyl        peroxypivalate,

and

-   -   a compound of the formula (III), preferably of the formula        (IIIa).

Preferred mixtures of the invention comprise or consist of

-   -   one or more radical initiators of the formula (IV) selected from        the group consisting of tert-butyl peroxypivalate, tert-amyl        peroxypivalate, tert-butyl peroxyneodecanoate,        1,1,3,3-tetramethylbutyl peroxyneodecanoate,        tert-butylperoxy-2-ethylhexanoate, 1,1,3,3-tetramethylbutyl        peroxy-2-ethyl-hexanoate, tert-amyl peroxyneodecanoate, cumyl        peroxyneodecanoate, cumyl peroxyneoheptanoate, and cumyl        peroxypivalate,

and

-   -   a compound of the formula (II), preferably of the formula (IIa).

The process of the invention enables the preparation of thephosphorus-containing cyanohydrins of the formula (I) or (Ia) under mildreaction conditions, thereby giving the phosphorus-containingcyanohydrins of the formula (I) or (Ia) in very good yields, which aresignificantly higher than as described in U.S. Pat. No. 4,521,348 or DE3047024.

Accordingly, when the process of the invention is implemented,disproportionation of reactants of the formula (II) or (IIa), forexample, is significantly lessened or largely prevented. Moreover, whenthe process of the invention is implemented, polymerization of thecompounds of the formula (III) or (IIIa) is significantly lessened orlargely prevented.

It has further been found that by premixing (parts) of the reactants ofthe formulae (II) and (III) or (IIa) and (IIIa), the polymerizationtendency of compounds of the formula (III) or (IIIa) can be reducedstill further.

In the context of the process of the invention it is advantageous to usethe cyanohydrins of the formula (III) or (IIIa) in a very high purity.The cyanohydrins of the formula (III) or (IIIa) are preferably used in apurity of greater than or equal to 90 wt %, more preferably of greaterthan or equal to 92 wt %.

In the context of the process of the invention it is advantageous tostabilize the cyanohydrins of the formula (III) or (IIIa) with one ormore acids, with preferably a pH in the range of 2-4 (measured at 25°C.) being established. The stabilizing acid used in this case may be,for example, phosphoric acid, polyphosphoric acid and/or acetic acid.

The phosphorus-containing cyanohydrins of the formula (I) or (Ia) thatare formed may be used as starting materials for the synthesis ofphosphorus-containing amino acids such as, for example, glufosinate (asynthesis route of this kind is described in more detail later onbelow). Another advantage of using cyanohydrins of the formula (III) or(IIIa) is therefore that it removes the need to introduce a protectinggroup for the OH group in the compounds of the formula (I) or (Ia) and(III) or (IIIa), and so makes the synthesis more simple overall.

In order to avoid unwanted secondary reactions and hence to achieve highyields, moreover, it is advantageous to use the phosphorus-containingreactant (II) or (IIa) in a molar excess, relative to the cyanohydrin ofthe formula (III) or (IIIa).

In the process of the invention, the molar ratio of the total amount ofthe phosphorus-containing reactant (II) or (IIa) used to the totalamount of the cyanohydrin of the formula (III) or (IIIa) used ispreferably in the range from 3:2 to 8:1, more preferably in the rangefrom 2:1 to 6:1, more preferably still in the range from 5:2 to 5:1,very preferably in the range from 2.8:1 to 4.0:1.

The process of the invention can be carried out either in batch mode orin continuous mode (i.e. continuous operating regime).

The process of the invention is carried out preferably with inertizing,more preferably in an inert gas atmosphere. Preferred inert gases inthis case are nitrogen and argon.

It is further possible to carry out the process of the invention undersuperatmospheric pressure or under reduced pressure.

The process of the invention can be carried out in a diluent.

As diluents it is possible in principle to use a variety of organicsolvents, preferably toluene, xylene, chlorobenzene, dichlorobenzene,dimethylformamide (DMF), dimethylacetamide, N-methyl-2-pyrrolidone(NMP), or mixtures of these organic solvents. The process of theinvention is preferably carried out without such solvents.

It may, however, be advantageous to carry out the process of theinvention in reaction product of the formula (I) or (Ia), already formedbeforehand, as diluent.

It may be advantageous to carry out the process of the invention in thereactant of the formula (II) or (IIa) as diluent, in which casepreferably a portion of the reactant of the formula (II) or (IIa) isintroduced as an initial charge to the reaction vessel or reactor.

Particularly in the case of continuous mode, it is advantageous to carryout the process of the invention in reaction product of the formula (I)or (Ia), already formed beforehand, or in a mixture of reaction productof the formula (I) or (Ia) and reactant of the formula (II) or (IIa), asdiluent.

The yields according to the process of the invention amount regularly to90-98%, based on the component of the formula (III) or (IIIa), andregularly to 88-96%, based on the component of the formula (II) or(IIa).

The purity of the products after purification, for example afterdistillative removal of the excess of component (II) or (IIa), amountsregularly to 90% to 96%. The recovered excess of the starting compound(II) can be used subsequently without further purification in the samereaction again.

In a further aspect, the present invention relates to particularphosphorus-containing cyanohydrins of the formula (Ib)

where R² is either n-butyl or n-pentyl, preferably n-butyl.

In our own investigations it has emerged that these two compounds can beprepared to particularly good effect with the process of the invention,and that these two compounds can be used with particular advantage inthe further reaction to give corresponding active agrochemicalingredients, preferably to give compounds with herbicidal activity, andmore particularly for the preparation of glufosinate and its salts.

This is true especially of the compound of the formula (Ib) whereR²=n-butyl, which is obtained according to the process of the inventionby reacting the phosphorus-containing reactant (IIa) where R¹=methyl andR²=n-butyl with acrolein cyanohydrin of the formula (IIIa).

Especially preferred, therefore, is the following compound (Ib-nBu):

Accordingly, the present invention also relates to the use of the twophosphorus-containing cyanohydrins of the formula (Ib) for preparingglufosinate and/or glufosinate salts.

Glufosinate salts in the context of the present invention are preferablyammonium salts, phosphonium salts, sulphonium salts, alkali metal saltsand alkaline earth metal salts of glufosinate.

Especially preferred in the context of the present invention areglufosinate, glufosinate-sodium and glufosinate-ammonium.

The reaction of the phosphorus-containing cyanohydrins of the formula(Ib) to form glufosinate and its salts may take place in analogy to theprocesses described from the prior art identified above.

In a further aspect, the present invention relates to the preparation ofglufosinate and/or glufosinate salts

characterized by reaction of a compound of the formula (Ib), by thefollowing step:

reaction of a compound of the formula (IIb)

where R² is n-butyl or n-pentyl

with acrolein cyanohydrin of the formula (IIIa)

where the reaction of (IIb) with (IIIa) takes place preferably accordingto the process of the invention described above.

The process for preparing glufosinate and/or glufosinate salts takesplace further preferably by reaction of a compound of the formula (Ib)with NH₃ to give compound (V)

where R² in each case is n-butyl or n-pentyl, preferably n-butyl,

and subsequent hydrolysis of compound (V) to give glufosinate and/or itssalts.

Glufosinate or glufosinate salt obtained by means of this process,preferably glufosinate-sodium salt or glufosinate-ammonium salt, isrelatively easy to purify and to isolate. One reason for this is thatfewer co-products and secondary products are produced in the processesof the invention, in comparison for example to the processes of U.S.Pat. Nos. 4,521,348 or 4,599,207.

With a view to what has been said above, therefore, the invention alsorelates to the new compounds of the formula (AMN)

where

Q is either OH or NH₂,

R² is either n-butyl or n-pentyl, preferably n-butyl,

and also to their use for preparing glufosinate and/or glufosinatesalts, more particularly glufosinate, glufosinate-sodium andglufosinate-ammonium.

EXAMPLES

Unless otherwise indicated, all figures are given by weight.

Example 1: Acrolein Cyanohydrin (Not Subject Matter of the PresentInvention)

100 g (0.791 mol) of acrolein cyanohydrin acetate (99% purity)(obtainable for example as described in U.S. Pat. No. 4,336,206) weremixed with 300 ml of dry methanol, with inertizing using nitrogen, andthe mixture was stirred at 20° C. for 6 days with 60 g of dried,previously activated* ion exchanger (Amberlyst 15, Rohm & Haas). Afterthe end of hydrolysis (GC check), the ion exchanger was removed byfiltration and washed with dry methanol. *The ion exchanger wasactivated by washing with half-concentrated hydrochloric acid, then withwater, and lastly with ethanol. After that the ion exchanger was driedunder reduced pressure at 60° C. (the ion exchanger can be used morethan once, i.e. used again, for the same reaction).

The combined filtrates were admixed with 5 drops of concentratedphosphoric acid (H₃PO₄) and then the solvent was removed on a rotaryevaporator at max. 30° C. and 0.5 mbar at the end. The residue obtainedwas 65.6 g of acrolein cyanohydrin (98% purity by GC and NMR),corresponding to a yield of 97.8% of theory. The resulting acroleincyanohydrin was used without further purification.

NMR (CDCl₃):

¹H: 3.97 ppm (s); 5.01 ppm (d); 5.47 ppm (d); 5.63 ppm (d); 5.95 ppm(m);

¹³C: 62.03 ppm; 116.41 ppm; 117.38 ppm; 131.53 ppm.

Example 2: n-Butyl (3-cyano-3-hydroxypropyl)methylphosphinate (ACM-H)

In a stirring apparatus with impeller stirrer, 20 g (0.1445 mol) ofmono-n-butyl methanephosphonate (98.5% purity, MPE, corresponding toformula (IIb) with R²=n-butyl) were introduced under nitrogen and heatedto 85° C. Added to this initial charge with vigorous stirring was 0.1 gof tert-butyl peroxyneodecanoate (radical initiator of the formula(IV)). Subsequently, the following mixtures were metered insimultaneously from two different syringe pumps: in one syringe pump, amixture of 5.0 g (0.036 mol) of MPE and 5.1 g of acrolein cyanohydrin(0.058 mol, purity: 94%), and in the other syringe pump a mixture of 15g (0.1084 mol) of MPE and 0.6 g of tert-butyl peroxyneodecanoate. Thetotal amount of tert-butyl peroxyneodecanoate was therefore 0.003 mol.The simultaneous metered introduction of the two mixtures into thestirring apparatus took place at constant temperature with vigorousstirring over a period of 2.5 hours. The resulting pale yellow reactionmixture, after the end of simultaneous metered introduction of the twomixtures, was stirred at 85° C. for 30 minutes more and then cooled.

According to ³¹P NMR, the reaction mixture contained 21.3 mol % of thedesired product (ACM-H) and 78.7 mol % of the MPE reactant.

According to ¹H NMR, the reaction mixture no longer contained anyacrolein cyanohydrin reactant.

30.0 g of the excess MPE were separated off (for the purpose of re-useas well) via a short-path evaporator distillation (outer jackettemperature of 105° C. and down to a pressure of 0.2 mbar). Remaining inthe bottom were 12.5 g of the desired n-butyl(3-cyano-3-hydroxypropyl)methylphosphinate product (ACM-H) with a purityof 95% (according to GC and NMR analysis). The yield of ACM-H thereforecorresponds to 93.6% of theory, based on acrolein cyanohydrin.

NMR (CDCl₃):

¹H: 0.95 ppm (t); 1.41 ppm (m); 1.52 ppm (d,d); 1.65 ppm (m); 2.0 ppm(m); 2.1 ppm (m); 4.0 ppm (m); 4.58 ppm (m); 6.15 ppm (s).

³¹P NMR: 55.5 ppm.

Example 3: n-Butyl (3-cyano-3-hydroxypropyl)methylphosphinate (ACM-H)

The batch size corresponded to that from Example 2, and the reactionprocedure was in analogy to Example 2, but using tert-butylperoxy-2-ethylhexanoate as radical initiator instead of tert-butylperoxyneodecanoate, and the amount of tert-butyl peroxy-2-ethylhexanoatewas 0.04 mol per mole of acrolein cyanohydrin. The reaction temperaturewas 88° C., the metering time 1.5 hours.

The reaction mixture also contained 3% of the acrolein cyanohydrinreactant. Acrolein cyanohydrin and excess MPE were removed as describedabove via a short-path evaporator distillation.

The yield of ACM-H found was 90% of theory, based on acroleincyanohydrin.

Example 4: n-Butyl (3-cyano-3-hydroxypropyl)methylphosphinate (ACM-H)

The batch size corresponded to that from Example 2, and the reactionprocedure was in analogy to Example 2, but using a mixture of tert-butylperoxy-2-ethylhexanoate and tert-butyl peroxyneodecanoate (in each case0.04 mol per mole of acrolein cyanohydrin) as radical initiator. Thereaction temperature was 88° C., the metering time 2 hours. Furtherwork-up was as described above.

The reaction mixture also contained traces of the acrolein cyanohydrinreactant.

The yield of ACM-H found was 93% of theory, based on acroleincyanohydrin.

Example 5: n-Butyl (3-cyano-3-hydroxypropyl)methylphosphinate (ACM-H)

Apparatus: First stirring vessel with heating jacket, two meteringpumps, and bottom drain valve, connected to a second stirring vessel;the stirring vessels were each equipped with an impeller stirrer.

Procedure: Auasi-Continuous Mode

Process Section 1:

In analogy to the experimental description in Example 2, the firststirring vessel was charged with 21 g of MPE under a nitrogenatmosphere, 0.1 g of tert-butyl peroxy-2-ethylhexanoate was added, andthe mixture was heated to 88° C. Thereafter, with vigorous stirring, twodifferent syringe pumps supplied metered feeds to this first stirringvessel, the first feed being a mixture of 8.06 g of acrolein cyanohydrinand 11.94 g of MPE, and the other feed being a mixture of 19 g of MPE,0.93 g of tert-butyl peroxyneodecanoate and 0.7 g of tert-butylperoxy-2-ethylhexanoate, the feeds taking place at constant temperatureover a period of 2 hours.

Process Section 2:

The reaction temperature was held further at 88° C. Subsequently, over afurther 2 hours, once again the same amounts of the same two mixtures ofacrolein cyanohydrin and MPE and of MPE, tert-butyl peroxyneodecanoateand tert-butyl peroxy-2-ethylhexanoate as described above were meteredseparately into the first stirring vessel via the same syringe pumps. Inaddition, a further 21 g of MPE were added dropwise and simultaneouslyfrom the first stirring vessel, by slow run-off through the bottomvalve, a constant run-off into the second stirring vessel, heated at 80°C., was ensured, and hence a constant fill level in the first reactorwas obtained as well.

Process Section 3:

After the end of the metered addition of the two mixtures and of theMPE, process section 2 was repeated once again.

In the reaction mixture subsequently obtained, there was no longer anyacrolein cyanohydrin.

For working up, the mixture was purified via a short-path evaporator ata jacket temperature of 115° C., 0.2-0.5 mbar. The excess MPE obtainedas distillate (115 g) was used again in later batches.

In the distillation bottom product there remained 58.6 g of n-butyl(3-cyano-3-hydroxypropyl)-methylphosphinate (94.8% crude yield), whichcould be used directly, i.e. without further purification, in thesubsequent reactions, for the preparation, for example, ofglufosinate-ammonium.

Example 6: n-Butyl (3-cyano-3-hydroxypropyl)methylphosphinate (ACM-H)

In a jacketed stirring vessel inertized using nitrogen and possessingthermometer, impeller stirrer and a bottom drain valve whose drain ledinto a heatable flask fitted with stirrer, the initiating reaction wasfirst of all carried out.

Initiating Reaction:

First of all 27 g of MPE were introduced and heated to 76° C. Thereafter0.1 g of initiator (1,1,3,3-tetramethylbutyl peroxyneodecanoate,acquired commercially as Trigonox® 423) was added. Subsequently, bymeans of two different syringe pumps, the following mixtures weremetered in simultaneously: in one syringe pump, a mixture of 9.7 g (97%purity) of acrolein cyanohydrin and 10.0 g of MPE, and simultaneously,in the other syringe pump, a mixture of 18.0 g of MPE and 2.4 g ofTrigonox® 423. The two mixtures were metered in at a uniform rate over 2hours, the temperature in the jacketed stirring vessel being held at 76°C.

Continuous Reaction Regime:

As described above, two mixtures were metered subsequently into thereaction vessel simultaneously and at a uniform rate over 6 hours, atthe same temperature:

Via a first pump, a mixture of 29.1 g of acrolein cyanohydrin and 30 gof MPE, and, via a second pump, a mixture of 54 g of MPE and 7.2 g ofTrigonox® 423 were metered into the reaction vessel. Simultaneously overthe same period of time, from a third metering vessel, a total of 81 gof MPE were added dropwise at a uniform rate. In order to keep aconstant fill level in the reaction vessel, a total of 195 g of theresultant reaction mixture were drained off through the bottom valveinto the flask which was maintained at 76° C. and provided with astirrer, throughout the duration of metering.

The reaction mixture was pale yellow and clear. After an after-reactiontime of around 15 minutes, the reaction mixtures were combined. Forworking up, the low-boiling components (including the excess MPE) weredistilled off via a short-path evaporator (0.2 mbar/115° C.). The crudeproduct remaining in the bottom can be used directly in this form forfurther reactions. 101.8 g of product (the GC purity of ACM-H was 9.15%)were obtained, corresponding to a yield of 94% of theory, based onacrolein cyanohydrin.

Example 7: Ammonium D,L-homoalanin-4-yl(methyl)phosphinate(Glufosinate-Ammonium)

From 218 g (0.885 mol) of n-butyl(3-cyano-3-hydroxypropyl)methylphosphinate (purity: 89%), furtherreaction was carried out with ammonia and with hydrochloric acid,similarly to the processes described in U.S. Pat. No. 6,359,162B1 or CN102399240A. Lastly, ammonia was added, giving an aqueous solution of theammonium salt.

Obtained in this way were 742.2 g of an aqueous solution containing22.5% of glufosinate-ammonium, corresponding to a yield of 95.2% oftheory.

The invention claimed is:
 1. An apparatus comprising a first mixture ofone or more compounds of the formula (IV) and one or more compounds ofthe formula (II) in a vessel and a second mixture comprising: one ormore compounds of the formula (II) and one or more compounds of theformula (III) in a separate vessel, where the compounds of the formula(II) and (III) are as follows:

R¹ is (C₁-C₁₂)-alkyl, (C₁-C₁₂)-haloalkyl, (C₆-C₁₀)-aryl,(C₆-C₁₀)-haloaryl, (C₇-C₁₀)-aralkyl, (C₇-C₁₀)-haloaralkyl,(C₄-C₁₀)-cycloalkyl or (C₄-C₁₀)-halocycloalkyl, R² is (C₁-C₁₂)-alkyl,(C₁-C₁₂)-haloalkyl, (C₆-C₁₀)-aryl, (C₆-C₁₀)-haloaryl, (C₇-C₁₀)-aralkyl,(C₇-C₁₀)-haloaralkyl, (C₄-C₁₀)-cycloalkyl or (C₄-C₁₀)-halocycloalkyl, R³and R⁴ are in each case independently of one another hydrogen,(C₁-C₄)-alkyl, phenyl or benzyl, X is oxygen or sulphur, and n is 0 or 1and the compounds of the formula (IV) have the structure as follows:

where R⁵ is methyl, ethyl, 2,2-dimethylpropyl or phenyl, R⁶independently at each occurrence is (C₁-C₁₀)-alkyl, and R⁷ is hydrogenor (C₁-C₁₀)-alkyl.
 2. The apparatus according to claim 1, wherein thesecond mixture contains no compound of the formula (IV) and/or nocompound of the formula (I), wherein the compound of the formula (I) hasthe structure as follows:


3. The apparatus according to claim 1, where the compounds of theformula (II) and (III) have the structure as follows:

where: R¹ is (C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl, (C₆-C₈)-aryl,(C₆-C₈)-haloaryl, (C₇-C₁₀)-aralkyl, (C₇-C₁₀)-haloaralkyl,(C₅-C₈)-cycloalkyl or (C₅-C₈)-halocycloalkyl, R² is (C₁-C₆)-alkyl,(C₁-C₆)-haloalkyl, (C₆-C₈)-aryl, (C₆-C₈)-haloaryl, (C₇-C₁₀)-aralkyl,(C₇-C₁₀)-haloaralkyl, (C₅-C₈)-cycloalkyl or (C₅-C₈)-halocycloalkyl andthe compounds of the formula (IV) are selected from the group consistingof tert-butyl peroxypivalate, tert-amyl peroxypivalate, tert-butylperoxyneodecanoate, 1,1,3,3-tetramethylbutyl peroxyneodecanoate,tert-butylperoxy-2-ethylhexanoate, 1,1,3,3-tetramethylbutylperoxy-2-ethylhexanoate, tert-amyl peroxyneodecanoate, cumylperoxyneodecanoate, cumyl peroxyneoheptanoate, and cumyl peroxypivalate.4. The apparatus according to claim 1, wherein R⁶ independently at eachoccurrence is (C₁-C₆)-alkyl, and R⁷ is hydrogen or (C₁-C₆)-alkyl.
 5. Theapparatus according to claim 1, wherein R¹ is (C₁-C₄)-alkyl or(C₁-C₄)-haloalkyl, R² is (C₁-C₆)-alkyl or (C₁-C₆)-haloalkyl, R³ and R⁴are in each case independently of one another hydrogen or methyl, X isoxygen, and n is
 1. 6. The apparatus according to claim 1, wherein R¹ ismethyl or ethyl, R² is (C₃-C₆)-alkyl, R³ and R⁴ are hydrogen or methyl,n is 1, and X is oxygen.
 7. The apparatus according to claim 1, whereinR¹ is methyl, R² is n-butyl or n-pentyl, R³ and R⁴ are hydrogen, n is 1,and X is oxygen.
 8. The apparatus according to claim 1, wherein R³ andR⁴ are in each case independently of one another hydrogen or methyl, andthe compounds of the formula (IV) are selected from the group consistingof tert-butyl peroxyneodecanoate, 1,1,3,3-tetramethylbutylperoxyneodecanoate, tert-butylperoxy-2-ethylhexanoate,1,1,3,3-tetramethylbutyl peroxy-2-ethylhexanoate, and cumylperoxyneodecanoate.
 9. The apparatus according to claim 1, wherein R³and R⁴ are hydrogen, and the compounds of the formula (IV) are selectedfrom the group consisting of 1,1,3,3-tetramethylbutylperoxyneodecanoate, tert-butyl peroxyneodecanoate, andtert-butylperoxy-2-ethylhexanoate.
 10. The apparatus according to claim1, wherein the compounds of the formula (IV) are selected from the groupconsisting of tert-butyl peroxyneodecanoate, 1,1,3,3-tetramethylbutylperoxyneodecanoate, tert-butylperoxy-2-ethylhexanoate,1,1,3,3-tetramethylbutyl peroxy-2-ethylhexanoate, and cumylperoxyneodecanoate.
 11. The apparatus according to claim 1, wherein thecompounds of the formula (IV) are selected from the group consisting of1,1,3,3-tetramethylbutyl peroxyneodecanoate, tert-butylperoxyneodecanoate, and tert-butylperoxy-2-ethylhexanoate.
 12. Anapparatus comprising a first mixture of one or more compounds of theformula (IV) and one or more compounds of the formula (III) in a vesseland a second mixture comprising one or more compounds of the formula(II) and one or more compounds of the formula (III) in a separatevessel, where the compounds of the formula (II) and (III) are asfollows:

R¹ is (C₁-C₁₂)-alkyl, (C₁-C₁₂)-haloalkyl, (C₆-C₁₀)-aryl,(C₆-C₁₀)-haloaryl, (C₇-C₁₀)-aralkyl, (C₇-C₁₀)-haloaralkyl,(C₄-C₁₀)-cycloalkyl or (C₄-C₁₀)-halocycloalkyl, R² is (C₁-C₁₂)-alkyl,(C₁-C₁₂)-haloalkyl, (C₆-C₁₀)-aryl, (C₆-C₁₀)-haloaryl, (C₇-C₁₀)-aralkyl,(C₇-C₁₀)-haloaralkyl, (C₄-C₁₀)-cycloalkyl or (C₄-C₁₀)-halocycloalkyl, R³and R⁴ are in each case independently of one another hydrogen,(C₁-C₄)-alkyl, phenyl or benzyl, X is oxygen or sulphur, and n is 0 or 1and the compounds of the formula (IV) have the structure as follows:

where R⁵ is methyl, ethyl, 2,2-dimethylpropyl or phenyl, R⁶independently at each occurrence is (C₁-C₁₀)-alkyl, and R⁷ is hydrogenor (C₁-C₁₀)-alkyl.
 13. The apparatus according to claim 12, wherein thesecond mixture contains no compound of the formula (IV) and/or nocompound of the formula (I), wherein the compound of the formula (I) hasthe structure as follows:


14. The apparatus according to claim 12, wherein R⁶ independently ateach occurrence is (C₁-C₄)-alkyl, and R⁷ is hydrogen or (C₁-C₄)-alkyl.15. The apparatus according to claim 12, wherein R¹ is (C₁-C₄)-alkyl or(C₁-C₄)-haloalkyl, R² is (C₁-C₆)-alkyl or (C₁-C₆)-haloalkyl, R³ and R⁴are in each case independently of one another hydrogen or methyl, X isoxygen, and n is
 1. 16. The apparatus according to claim 12, wherein R¹is methyl or ethyl, R² is (C₃-C₆)-alkyl, R³ and R⁴ are hydrogen ormethyl, n is 1, and X is oxygen.
 17. The apparatus according to claim12, wherein R¹ is methyl, R² is n-butyl, R³ and R⁴ are hydrogen, n is 1,and X is oxygen.
 18. The apparatus according to claim 12, where thecompounds of the formula (II) and (III) have the structure as follows:

where: R¹ is (C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl, (C₆-C₈)-aryl,(C₆-C₈)-haloaryl, (C₇-C₁₀)-aralkyl, (C₇-C₁₀)-haloaralkyl,(C₅-C₈)-cycloalkyl or (C₅-C₈)-halocycloalkyl, R² is (C₁-C₆)-alkyl,(C₁-C₆)-haloalkyl, (C₆-C₈)-aryl, (C₆-C₈)-haloaryl, (C₇-C₁₀)-aralkyl,(C₇-C₁₀)-haloaralkyl, (C₅-C₈)-cycloalkyl or (C₅-C₈)-halocycloalkyl andthe compounds of the formula (IV) are selected from the group consistingof tert-butyl peroxypivalate, tert-amyl peroxypivalate, tert-butylperoxyneodecanoate, 1,1,3,3-tetramethylbutyl peroxyneodecanoate,tert-butylperoxy-2-ethylhexanoate, 1,1,3,3-tetramethylbutylperoxy-2-ethylhexanoate, tert-amyl peroxyneodecanoate, cumylperoxyneodecanoate, cumyl peroxyneoheptanoate, and cumyl peroxypivalate.19. The apparatus according to claim 12, wherein the compounds of theformula (IV) are selected from the group consisting of tert-butylperoxyneodecanoate, 1,1,3,3-tetramethylbutyl peroxyneodecanoate,tert-butylperoxy-2-ethylhexanoate, 1,1,3,3-tetramethylbutylperoxy-2-ethylhexanoate, and cumyl peroxyneodecanoate.
 20. The apparatusaccording to claim 12, wherein the compounds of the formula (IV) areselected from the group consisting of 1,1,3,3-tetramethylbutylperoxyneodecanoate, tert-butyl peroxyneodecanoate, andtert-butylperoxy-2-ethylhexanoate.